Herpes Zoster

⚙

Pathophysiology

2

Ganglionic VZV Latency and Reactivation Under Waning T-Cell Immunity

Following primary varicella infection, VZV persists latently in dorsal root, trigeminal, geniculate, and autonomic ganglionic neurons. Immunosenescence or cellular immunosuppression allows latent VZV to reactivate, replicate within ganglionic neurons, and spread anterogradely down sensory axons to the corresponding cutaneous dermatome and central nervous system targets.

neuron CL:0000540 T cell CL:0000084

viral latency GO:0019042 ⚠ ABNORMAL viral genome replication GO:0019079 ↑ INCREASED

dorsal root ganglion UBERON:0000044 trigeminal ganglion UBERON:0001675

Downstream

Dermatomal Ganglionitis, Neuroinflammation, and Postherpetic Neuralgia Intraganglionic viral replication and anterograde axonal transport trigger dermatomal skin lesions and sensory ganglionitis.

Show evidence (1 reference)

PMID:37632006 SUPPORT Human clinical

"Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."

Confirms ganglionic neuronal latency and subsequent reactivation to produce herpes zoster.

Dermatomal Ganglionitis, Neuroinflammation, and Postherpetic Neuralgia

Active VZV replication in sensory ganglia and peripheral nerves provokes hemorrhagic ganglionitis, neuronal injury, and demyelination that manifest acutely as dermatomal vesicular rash and acute herpetic pain, and persist as chronic neuropathic pain (postherpetic neuralgia), cranial nerve palsies, myelitis, meningoencephalitis, or cerebral VZV vasculopathy.

neuron CL:0000540

inflammatory response GO:0006954 ↑ INCREASED

dorsal root ganglion UBERON:0000044 zone of skin UBERON:0000014 cerebral artery UBERON:0004449

Downstream

Skin rash Anterograde axonal delivery of VZV to epidermis produces the unilateral dermatomal vesicular rash.

Neuralgia Sensory ganglionic damage and central sensitization produce acute zoster pain and postherpetic neuralgia.

Show evidence (1 reference)

PMID:37632006 SUPPORT Human clinical

"While the most frequent reactivation syndrome is herpes zoster, this may be followed by the serious and painful post-herpetic neuralgia (PHN) and by many other neurological conditions. Prominent among these conditions is a VZV vasculopathy, but the role of VZV in causing giant cell arteritis..."

Details the neurological complications of VZV reactivation including postherpetic neuralgia, VZV vasculopathy, cranial neuropathies, myelitis, and meningoencephalitis.

⬡

Pathograph

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Phenotypes

2

Immune 1

Skin rash VERY_FREQUENT Vesicular eruption HP:0033697

Show evidence (2 references)

PMID:37588338 SUPPORT Human clinical

"Zoster, commonly known as shingles, is a syndrome caused by the reactivation of the varicella-zoster virus (VZV) that results in characteristic vesicular eruptions in a unilateral dermatomal distribution."

Directly establishes that VZV reactivation causes characteristic vesicular eruptions in a unilateral dermatomal distribution.

PMID:38416279 SUPPORT Human clinical

"Herpes zoster (HZ; shingles) is a painful, cutaneous disease caused by reactivation of the varicella zoster virus, which causes varicella (chickenpox) typically during childhood."

Directly characterizes herpes zoster as a painful cutaneous disease caused by VZV reactivation.

Constitutional 1

Neuralgia FREQUENT HP:0033345

Show evidence (1 reference)

PMID:38416279 SUPPORT Human clinical

"The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and..."

Documents debilitating neuropathic pain and postherpetic neuralgia as primary complications of herpes zoster.

💊

Medical Actions

1

Adjuvanted Recombinant Zoster Vaccine (RZV / Shingrix, VZV gE + AS01B)

Action: vaccination Ontology label: Vaccination NCIT:C15346

Platform: Vaccine

Two-dose recombinant subunit vaccine containing varicella-zoster virus glycoprotein E (gE) and the AS01B liposomal adjuvant system (MPL and QS-21). In phase 3 trials, HZ/su achieved 97.2% overall vaccine efficacy against herpes zoster in adults >=50 years of age (ZOE-50) and 91.3% efficacy against herpes zoster plus 88.8% efficacy against postherpetic neuralgia in adults >=70 years of age (pooled ZOE-50/ZOE-70), overcoming the age-related efficacy decline seen with live-attenuated zoster vaccine.

Mechanism Target:

INHIBITS Ganglionic VZV Latency and Reactivation Under Waning T-Cell Immunity — AS01B-adjuvanted gE immunization restores VZV-specific CD4+ T-cell and humoral immunity that suppresses clinical VZV reactivation from ganglionic latency.

Show evidence (1 reference)

PMID:25916341 SUPPORT INDIRECT Human clinical

"During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2%..."

Demonstrates 97.2% efficacy of HZ/su in preventing herpes zoster reactivation in adults aged 50 years or older.

Effect differs by subgroup:

comorbidity immunocompromised individuals vs immunocompetent older adults — larger effect on herpes zoster incidence, severity, and absolute risk reduction from non-live recombinant vaccination

Immunocompromised individuals experience higher herpes zoster incidence, severity, and recurrence risk, and non-live recombinant adjuvanted zoster vaccination is specifically indicated where live-attenuated vaccines are contraindicated.

Show evidence (1 reference)

PMID:38416279 SUPPORT Human clinical

"The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and..."

Documents increased herpes zoster severity and burden in immunocompromised individuals.

Show evidence (2 references)

PMID:25916341 SUPPORT Human clinical

"During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2%..."

Pivotal ZOE-50 trial showing 97.2% vaccine efficacy against herpes zoster.

PMID:27626517 SUPPORT Human clinical

"In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001)."

Pivotal ZOE-70 pooled analysis demonstrating 91.3% efficacy against HZ and 88.8% efficacy against PHN in adults >=70 years old.

🔬

Diagnosis

1

Clinical and Virological Confirmation of Herpes Zoster

Confirmation of suspected herpes zoster episodes by clinical evaluation of the unilateral dermatomal rash and laboratory testing (VZV DNA PCR, Tzanck smear of herpetic vesicle specimens, or VZV-specific IgM and IgA serology in inconclusive or atypical presentations).

diagnostic procedure NCIT:C18020

Show evidence (1 reference)

PMID:37588338 SUPPORT Human clinical

"The diagnosis of shingles is often made clinically, based on the visually apparent and clear temporal-regional pattern of the rash. In cases where the clinical assessment is inconclusive, traditional methods such as VZV DNA PCR, Tzanck smear using herpetic vesicle specimens, or the detection of..."

Documents clinical diagnosis from the rash pattern and laboratory confirmation by VZV DNA PCR, Tzanck smear, or VZV IgM/IgA serology.

📈

Progression

3

Ganglionic Latency and Prodromal Reactivation Phase

After primary varicella infection in childhood, VZV remains latent in ganglionic neurons for a variable period until declining cell-mediated immunity permits viral reactivation and intraganglionic replication.

Show evidence (1 reference)

PMID:37632006 SUPPORT Human clinical

"Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."

Establishes the variable latency period in ganglionic neurons prior to reactivation as herpes zoster.

Acute Dermatomal Eruptive Phase

Reactivated virus travels down sensory nerves to the skin, producing an acute painful unilateral dermatomal rash.

Show evidence (1 reference)

PMID:38416279 SUPPORT Human clinical

"Herpes zoster (HZ; shingles) is a painful, cutaneous disease caused by reactivation of the varicella zoster virus, which causes varicella (chickenpox) typically during childhood."

Characterizes the acute painful cutaneous presentation of herpes zoster following VZV reactivation.

Chronic Postherpetic Neuralgia and Potential Recurrence Phase

Following resolution of the acute rash, patients may develop persistent postherpetic neuralgia (PHN) and carry a 1.2% to 9.6% long-term risk of herpes zoster recurrence.

Show evidence (1 reference)

PMID:38416279 SUPPORT Human clinical

"Studies in general populations of immunocompetent or immunocompetent/immunosuppressed (mixed) populations with an initial HZ episode estimate that approximately 1.2-9.6% of individuals may experience HZ recurrence, with an incidence rate of 1.7-16.6 cases per 1000 person-years."

Quantifies the long-term recurrence rate after an initial herpes zoster episode.

📊

Prevalence

1

General population

Lifetime prevalence Common

Approximately one in three individuals experience at least one episode of herpes zoster during their lifetime, and 1.2% to 9.6% of individuals with an initial episode experience recurrence (1.7 to 16.6 cases per 1,000 person-years).

Show evidence (2 references)

PMID:38416279 SUPPORT Human clinical

"The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and..."

Documents a lifetime occurrence of approximately one in three individuals and increased severity in immunocompromised hosts.

PMID:38416279 SUPPORT Human clinical

"Studies in general populations of immunocompetent or immunocompetent/immunosuppressed (mixed) populations with an initial HZ episode estimate that approximately 1.2-9.6% of individuals may experience HZ recurrence, with an incidence rate of 1.7-16.6 cases per 1000 person-years."

Quantifies herpes zoster recurrence rates (1.2% to 9.6%) in general and mixed populations.

🦠

Infectious Agent

1

Varicella-zoster virus (Human alphaherpesvirus 3)

Neurotropic human alphaherpesvirus that causes varicella (chickenpox) during primary infection and establishes lifelong latency in sensory and autonomic ganglionic neurons, reactivating to cause herpes zoster.

Human alphaherpesvirus 3 NCBITaxon:10335

Show evidence (1 reference)

PMID:37632006 SUPPORT Human clinical

"Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."

Establishes VZV latency in ganglionic neurons and reactivation as the etiology of herpes zoster.

↔️

Transmission

1

Endogenous reactivation from ganglionic latency

Herpes zoster arises by endogenous reactivation of latent varicella-zoster virus from sensory and autonomic ganglionic neurons established during prior primary varicella infection.

Show evidence (1 reference)

PMID:37632006 SUPPORT Human clinical

"Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."

Establishes that herpes zoster develops via endogenous reactivation of latent VZV in ganglionic neurons following primary varicella infection.

{ }

Source YAML

click to show

name: Herpes Zoster
creation_date: '2026-10-25T20:15:00Z'
category: Infectious Disease
description: >-
  Herpes zoster (shingles) is a neurocutaneous disease caused by the
  reactivation of latent varicella-zoster virus (VZV; human alphaherpesvirus 3)
  from cranial nerve, dorsal root, or autonomic ganglionic neurons when
  VZV-specific cell-mediated immunity declines with advancing age or
  immunosuppression. Reactivated virus replicates in ganglionic neurons and
  travels anterogradely along sensory axons to the innervated dermatome,
  producing a painful unilateral vesicular rash and ganglionic inflammation that
  frequently progresses to postherpetic neuralgia (PHN) and can be complicated
  by VZV vasculopathy, cranial neuropathies, myelitis, or meningoencephalitis.
disease_term:
  preferred_term: herpes zoster
  term:
    id: MONDO:0005609
    label: herpes zoster
parents:
- Viral Disease
synonyms:
- Shingles
- Zona
- Acute posterior ganglionitis
infectious_agent:
- name: Varicella-zoster virus (Human alphaherpesvirus 3)
  description: >-
    Neurotropic human alphaherpesvirus that causes varicella (chickenpox) during
    primary infection and establishes lifelong latency in sensory and autonomic
    ganglionic neurons, reactivating to cause herpes zoster.
  infectious_agent_term:
    preferred_term: Human alphaherpesvirus 3
    term:
      id: NCBITaxon:10335
      label: Human alphaherpesvirus 3
  evidence:
  - reference: PMID:37632006
    reference_title: "The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."
    explanation: Establishes VZV latency in ganglionic neurons and reactivation as the etiology of herpes zoster.
agent_life_cycle:
  description: >-
    Varicella-zoster virus is an exclusively human herpesvirus that establishes
    latency in dorsal root, cranial nerve (trigeminal and geniculate), and
    autonomic ganglia after primary varicella infection and reactivates
    endogenously to cause herpes zoster.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: obligate human reservoir and definitive host
transmission:
- name: Endogenous reactivation from ganglionic latency
  description: >-
    Herpes zoster arises by endogenous reactivation of latent varicella-zoster
    virus from sensory and autonomic ganglionic neurons established during
    prior primary varicella infection.
  evidence:
  - reference: PMID:37632006
    reference_title: "The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."
    explanation: Establishes that herpes zoster develops via endogenous reactivation of latent VZV in ganglionic neurons following primary varicella infection.
prevalence:
- population: General population
  measure_type: LIFETIME_PREVALENCE
  prevalence_class: COMMON
  notes: >-
    Approximately one in three individuals experience at least one episode of
    herpes zoster during their lifetime, and 1.2% to 9.6% of individuals with
    an initial episode experience recurrence (1.7 to 16.6 cases per 1,000
    person-years).
  evidence:
  - reference: PMID:38416279
    reference_title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and rarely, stroke, and increased severity in immunocompromised individuals."
    explanation: Documents a lifetime occurrence of approximately one in three individuals and increased severity in immunocompromised hosts.
  - reference: PMID:38416279
    reference_title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Studies in general populations of immunocompetent or immunocompetent/immunosuppressed (mixed) populations with an initial HZ episode estimate that approximately 1.2-9.6% of individuals may experience HZ recurrence, with an incidence rate of 1.7-16.6 cases per 1000 person-years."
    explanation: Quantifies herpes zoster recurrence rates (1.2% to 9.6%) in general and mixed populations.
progression:
- phase: Ganglionic Latency and Prodromal Reactivation Phase
  notes: >-
    After primary varicella infection in childhood, VZV remains latent in
    ganglionic neurons for a variable period until declining cell-mediated
    immunity permits viral reactivation and intraganglionic replication.
  evidence:
  - reference: PMID:37632006
    reference_title: "The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."
    explanation: Establishes the variable latency period in ganglionic neurons prior to reactivation as herpes zoster.
- phase: Acute Dermatomal Eruptive Phase
  notes: >-
    Reactivated virus travels down sensory nerves to the skin, producing an
    acute painful unilateral dermatomal rash.
  evidence:
  - reference: PMID:38416279
    reference_title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Herpes zoster (HZ; shingles) is a painful, cutaneous disease caused by reactivation of the varicella zoster virus, which causes varicella (chickenpox) typically during childhood."
    explanation: Characterizes the acute painful cutaneous presentation of herpes zoster following VZV reactivation.
- phase: Chronic Postherpetic Neuralgia and Potential Recurrence Phase
  notes: >-
    Following resolution of the acute rash, patients may develop persistent
    postherpetic neuralgia (PHN) and carry a 1.2% to 9.6% long-term risk of
    herpes zoster recurrence.
  evidence:
  - reference: PMID:38416279
    reference_title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Studies in general populations of immunocompetent or immunocompetent/immunosuppressed (mixed) populations with an initial HZ episode estimate that approximately 1.2-9.6% of individuals may experience HZ recurrence, with an incidence rate of 1.7-16.6 cases per 1000 person-years."
    explanation: Quantifies the long-term recurrence rate after an initial herpes zoster episode.
pathophysiology:
- name: Ganglionic VZV Latency and Reactivation Under Waning T-Cell Immunity
  description: >-
    Following primary varicella infection, VZV persists latently in dorsal root,
    trigeminal, geniculate, and autonomic ganglionic neurons. Immunosenescence
    or cellular immunosuppression allows latent VZV to reactivate, replicate
    within ganglionic neurons, and spread anterogradely down sensory axons to
    the corresponding cutaneous dermatome and central nervous system targets.
  role: trigger
  biological_scale: CELLULAR
  locations:
  - preferred_term: dorsal root ganglion
    term:
      id: UBERON:0000044
      label: dorsal root ganglion
  - preferred_term: trigeminal ganglion
    term:
      id: UBERON:0001675
      label: trigeminal ganglion
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  biological_processes:
  - preferred_term: viral latency
    modifier: ABNORMAL
    term:
      id: GO:0019042
      label: viral latency
  - preferred_term: viral genome replication
    modifier: INCREASED
    term:
      id: GO:0019079
      label: viral genome replication
  evidence:
  - reference: PMID:37632006
    reference_title: "The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles)."
    explanation: Confirms ganglionic neuronal latency and subsequent reactivation to produce herpes zoster.
  downstream:
  - target: Dermatomal Ganglionitis, Neuroinflammation, and Postherpetic Neuralgia
    description: Intraganglionic viral replication and anterograde axonal transport trigger dermatomal skin lesions and sensory ganglionitis.
    causal_link_type: DIRECT
- name: Dermatomal Ganglionitis, Neuroinflammation, and Postherpetic Neuralgia
  description: >-
    Active VZV replication in sensory ganglia and peripheral nerves provokes
    hemorrhagic ganglionitis, neuronal injury, and demyelination that manifest
    acutely as dermatomal vesicular rash and acute herpetic pain, and persist as
    chronic neuropathic pain (postherpetic neuralgia), cranial nerve palsies,
    myelitis, meningoencephalitis, or cerebral VZV vasculopathy.
  role: central_effector
  biological_scale: TISSUE
  locations:
  - preferred_term: dorsal root ganglion
    term:
      id: UBERON:0000044
      label: dorsal root ganglion
  - preferred_term: zone of skin
    term:
      id: UBERON:0000014
      label: zone of skin
  - preferred_term: cerebral artery
    term:
      id: UBERON:0004449
      label: cerebral artery
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:37632006
    reference_title: "The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "While the most frequent reactivation syndrome is herpes zoster, this may be followed by the serious and painful post-herpetic neuralgia (PHN) and by many other neurological conditions. Prominent among these conditions is a VZV vasculopathy, but the role of VZV in causing giant cell arteritis (GCA) is currently controversial. VZV reactivation can also cause segmental motor weakness, myelitis, cranial nerve syndromes, Guillain-Barre syndrome, meningoencephalitis, and zoster sine herpete, where a neurological syndrome occurs in the absence of the zoster rash."
    explanation: Details the neurological complications of VZV reactivation including postherpetic neuralgia, VZV vasculopathy, cranial neuropathies, myelitis, and meningoencephalitis.
  downstream:
  - target: Skin rash
    description: Anterograde axonal delivery of VZV to epidermis produces the unilateral dermatomal vesicular rash.
  - target: Neuralgia
    description: Sensory ganglionic damage and central sensitization produce acute zoster pain and postherpetic neuralgia.
phenotypes:
- name: Skin rash
  category: Dermatological
  frequency: VERY_FREQUENT
  description: Painful unilateral dermatomal vesicular cutaneous eruption is the classic clinical manifestation of herpes zoster.
  phenotype_term:
    preferred_term: Vesicular eruption
    term:
      id: HP:0033697
      label: Vesicular eruption
  evidence:
  - reference: PMID:37588338
    reference_title: "Zoster Sine Herpete: Confirmatory Diagnosis Using Varicella-Zoster Virus DNA Polymerase Chain Reaction Analysis of Intact Skin Scrapings."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Zoster, commonly known as shingles, is a syndrome caused by the reactivation of the varicella-zoster virus (VZV) that results in characteristic vesicular eruptions in a unilateral dermatomal distribution."
    explanation: Directly establishes that VZV reactivation causes characteristic vesicular eruptions in a unilateral dermatomal distribution.
  - reference: PMID:38416279
    reference_title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Herpes zoster (HZ; shingles) is a painful, cutaneous disease caused by reactivation of the varicella zoster virus, which causes varicella (chickenpox) typically during childhood."
    explanation: Directly characterizes herpes zoster as a painful cutaneous disease caused by VZV reactivation.
- name: Neuralgia
  category: Neurological
  frequency: FREQUENT
  description: Acute dermatomal neuropathic pain and chronic postherpetic neuralgia (PHN) are the major debilitating manifestations of herpes zoster.
  phenotype_term:
    preferred_term: Neuralgia
    term:
      id: HP:0033345
      label: Neuralgia
  evidence:
  - reference: PMID:38416279
    reference_title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and rarely, stroke, and increased severity in immunocompromised individuals."
    explanation: Documents debilitating neuropathic pain and postherpetic neuralgia as primary complications of herpes zoster.
diagnosis:
- name: Clinical and Virological Confirmation of Herpes Zoster
  description: >-
    Confirmation of suspected herpes zoster episodes by clinical evaluation of
    the unilateral dermatomal rash and laboratory testing (VZV DNA PCR, Tzanck
    smear of herpetic vesicle specimens, or VZV-specific IgM and IgA serology in
    inconclusive or atypical presentations).
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:37588338
    reference_title: "Zoster Sine Herpete: Confirmatory Diagnosis Using Varicella-Zoster Virus DNA Polymerase Chain Reaction Analysis of Intact Skin Scrapings."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis of shingles is often made clinically, based on the visually apparent and clear temporal-regional pattern of the rash. In cases where the clinical assessment is inconclusive, traditional methods such as VZV DNA PCR, Tzanck smear using herpetic vesicle specimens, or the detection of serological markers with immunoglobulins like serum IgM and IgA antibodies can be employed to confirm the diagnosis."
    explanation: Documents clinical diagnosis from the rash pattern and laboratory confirmation by VZV DNA PCR, Tzanck smear, or VZV IgM/IgA serology.
treatments:
- name: Adjuvanted Recombinant Zoster Vaccine (RZV / Shingrix, VZV gE + AS01B)
  description: >-
    Two-dose recombinant subunit vaccine containing varicella-zoster virus
    glycoprotein E (gE) and the AS01B liposomal adjuvant system (MPL and QS-21).
    In phase 3 trials, HZ/su achieved 97.2% overall vaccine efficacy against
    herpes zoster in adults >=50 years of age (ZOE-50) and 91.3% efficacy
    against herpes zoster plus 88.8% efficacy against postherpetic neuralgia in
    adults >=70 years of age (pooled ZOE-50/ZOE-70), overcoming the age-related
    efficacy decline seen with live-attenuated zoster vaccine.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  target_mechanisms:
  - target: Ganglionic VZV Latency and Reactivation Under Waning T-Cell Immunity
    treatment_effect: INHIBITS
    description: >-
      AS01B-adjuvanted gE immunization restores VZV-specific CD4+ T-cell and
      humoral immunity that suppresses clinical VZV reactivation from ganglionic
      latency.
    evidence:
    - reference: PMID:25916341
      reference_title: "Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001)."
      explanation: Demonstrates 97.2% efficacy of HZ/su in preventing herpes zoster reactivation in adults aged 50 years or older.
  effect_modifiers:
  - effect_modifier_type: COMORBIDITY
    stratum: immunocompromised individuals
    comparator_stratum: immunocompetent older adults
    modified_outcome: herpes zoster incidence, severity, and absolute risk reduction from non-live recombinant vaccination
    effect_in_stratum: LARGER_EFFECT
    description: >-
      Immunocompromised individuals experience higher herpes zoster incidence,
      severity, and recurrence risk, and non-live recombinant adjuvanted
      zoster vaccination is specifically indicated where live-attenuated
      vaccines are contraindicated.
    evidence:
    - reference: PMID:38416279
      reference_title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and rarely, stroke, and increased severity in immunocompromised individuals."
      explanation: Documents increased herpes zoster severity and burden in immunocompromised individuals.
  evidence:
  - reference: PMID:25916341
    reference_title: "Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001)."
    explanation: Pivotal ZOE-50 trial showing 97.2% vaccine efficacy against herpes zoster.
  - reference: PMID:27626517
    reference_title: "Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001)."
    explanation: Pivotal ZOE-70 pooled analysis demonstrating 91.3% efficacy against HZ and 88.8% efficacy against PHN in adults >=70 years old.
references:
- reference: PMID:25916341
  title: "Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults."
  findings: []
- reference: PMID:27626517
  title: "Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older."
  findings: []
- reference: PMID:37588338
  title: "Zoster Sine Herpete: Confirmatory Diagnosis Using Varicella-Zoster Virus DNA Polymerase Chain Reaction Analysis of Intact Skin Scrapings."
  findings: []
- reference: PMID:37632006
  title: "The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation."
  findings: []
- reference: PMID:38416279
  title: "Herpes Zoster Recurrence: A Narrative Review of the Literature."
  findings: []

📚

References & Deep Research

References

5

PMID:25916341

Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.

No top-level findings curated for this source.

PMID:27626517

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.

No top-level findings curated for this source.

PMID:37588338

Zoster Sine Herpete: Confirmatory Diagnosis Using Varicella-Zoster Virus DNA Polymerase Chain Reaction Analysis of Intact Skin Scrapings.

No top-level findings curated for this source.

PMID:37632006

The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation.

No top-level findings curated for this source.

PMID:38416279

Herpes Zoster Recurrence: A Narrative Review of the Literature.

No top-level findings curated for this source.

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